Pharmaceutical forms for the oral administration of mesna

ABSTRACT

The invention relates to pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 88% of mesna, produced by granulation with up to 15% of water, based on the amount of solid employed, and also tablets, film-coated tablets, pellets or granules comprising at least 80% of mesna, produced by direct compression or compaction without the use of organic solvents.

[0001] Mesna is a known antidote, which is employed for the prophylaxisof the urotoxicity of oxaphosphorines such as ifosphamide andcyclophosphamide. In addition to parenteral formulations, oralformulations are also already known.

[0002] Thus in U.S. Pat. No. 5,503,845, oral formulations in the form oftablets, pellets, capsules having an active compound content of upto >85% of mesna in combination with a preparation process of moistgranulation with more than 30% of water, based on the amount of thesolids employed, are described. Problems here are the long anduneconomical drying times to be expected as a result of the largeamounts of water. Moreover, high amounts of water also lead to activecompound instability.

[0003] Effervescent tablets with 10-80% of mesna are furthermoredisclosed in U.S. Pat. No. 5,358,718. U.S. Pat. No. 5,262,169 describestablets with 10-80% of mesna.

[0004] In both abovementioned patent specifications, the claimedcomposition is coupled with an alcoholic granulation process.

[0005] The use of organic liquids in granulation, however, is to beclassified as problematical, since these substances are usuallyenvironmentally harmful, and moreover special arrangements are neededfor employee protection.

[0006] EP 0468245 describes mesna tablets which contain 10-80% of mesna,in combination with various auxiliaries. Here too, a process for theproduction of these tablets by means of granulation in the presence oforganic solvents is described. The same problems apply as with theabovementioned US patents.

[0007] The object is thus to produce mesna tablets by means of a simple,economical production method and to do this, if possible, without theuse of organic solvents.

[0008] Since mesna is administered in high doses, it is necessary forthe oral mesna formulations to have an active compound content of over80%.

[0009] Surprisingly, it was possible to achieve the object mentioned byproducing pharmaceutical forms for oral administration in the form oftablets, film-coated tablets, pellets or granules comprising at least88% of mesna, by granulation with up to 15% of water, based on theamount of solid employed, or pharmaceutical forms for oraladministration in the form of tablets, film-coated tablets, pellets orgranules comprising at least 80% of mesna by direct compression orcompaction.

[0010] It is to be emphasized that the process for the production ofpharmaceutical forms for oral administration in the form of tablets,film-coated tablets, pellets or granules by granulation, directcompression or compaction manages without the use of organic solvents.

[0011] The invention is illustrated in greater detail by means of thefollowing working examples without, however, being restricted thereby.

EXAMPLE 1

[0012] Tablets with 100% of Mesna

[0013] 500 g of mesna are sieved and moistened with 97 g of water(=19.4% based on the solid). The mixture is then granulated, and driedat 40° C. on racks. The granules are compressed to give tablets. Weight:500 mg Breaking strength: 70-80 N Disintegration: <1.5 min.

EXAMPLE 2

[0014] Tablets with 88% of Mesna

[0015] Pure Aqueous Granulation with 5.6% of Water

[0016] 2.7 g of corn starch are dissolved in 3.3 g of water and swollenin 13.7 g of water.

[0017] 300 g of mesna are sieved and kneaded together with swollen cornstarch.

[0018] The moist mass is granulated and dried at 40° C. on racks. Thedried granules are mixed with 27.0 g of microcrystalline cellulose and6.0 g of corn starch. 2.7 g of magnesium stearate are then added andmixing is carried out again. Weight: 225.6 mg Breaking strength: 100 NDisintegration: <4 min.

EXAMPLE 3

[0019] Tablets with 81.6% of Mesna

[0020] Compaction.

[0021] 200 g of mesna are sieved together with 30.0 g of lactose and10.0 g of highly disperse silica and mixed. 5.0 g of magnesium stearateare then added and mixing is carried out again. The mass prepared inthis way is compressed to give pressed tablets. The pressed tablets arecomminuted and sieved. The material resulting in this way is mixed andprocessed to give tablets. Weight: 245 mg Breaking strength: 50 NDisintegration: <3 min.

1. Pharmaceutical forms for oral administration in the form of tablets,film-coated tablets, pellets or granules comprising at least 88% ofmesna, produced by granulation with up to 15% of water, based on theamount of solid employed.
 2. Pharmaceutical forms for oraladministration in the form of tablets, film-coated tablets, pellets orgranules comprising at least 80% of mesna, produced by directcompression or compaction.
 3. Process for the production ofpharmaceutical forms for oral administration in the form of tablets,film-coated tablets, pellets or granules comprising at least 88% ofmesna, according to claim 1, by granulation with up to 15% of water,based on the amount of solid employed, without the use of organicsolvents.
 4. Process for the production of pharmaceutical forms for oraladministration in the form of tablets, film-coated tablets, pellets orgranules comprising at least 80% of mesna, according to claim 2, bydirect compression or compaction without the use of organic solvents.